BACKGROUND:Inflammation is an important pathogenic factor that leads to thyroid follicular epithelial cells injury after Hashimoto's thyroiditis (HT). Recent studies proposed relationships between pyroptosis and apolipoproteins in HT. However, the molecular signatures involved in the pathophysiological changes that occur during the course of HT remain ambiguous. METHODS:The current study obtained thyroid tissues from HT patients and investigated the genes and pathways involved in HT by transcriptome sequencing analysis. Besides, ELISA, immunohistochemical staining, western blot analysis, LDH release assay and RNA interference were conducted to validate the expression levels of dysregulated proteins and underlying pathways. RESULTS:Transcriptomic analysis demonstrated that HT was associated with the enrichment of genes related to the inflammatory response, pyroptosis, and regulation of the lipid metabolic process. The transcription level of APOC1 gene ranked highest among apolipoproteins, and genes associated with the interleukin (IL)-18 signaling pathway and the NLRP3 inflammasome were upregulated. The expression levels of IL-18, NLRP3, and APOC1 proteins were increased in HT patients. Furthermore, in vitro studies using LPS-treated Nthy-ori 3-1 thyroid cells confirmed that APOC1 induced pyroptosis through TLR10/MyD88/NF-κB p65 dependent pathway. CONCLUSIONS:APOC1 probably participated in the pathogenesis of HT by mediating TFCs pyroptosis through TLR10/MyD88/NF-κB pathway.

Hashimoto's thyroiditis (HT) is a chronic autoimmune disorder primarily driven by T cell. The apoptosis of the follicular thyroid cells plays an important role in HT apart from the lymphocyte-mediated cytotoxicity. Advanced oxidation protein products (AOPPs), resulting from oxidative stress, are known to be involved in various inflammatory diseases. However, their role in HT development has not been explored. Here, we discovered that AOPP levels were significantly elevated in thyroid tissues of both HT patients (Ctrl 4.12 +/- 0.56, HT 30.00 +/- 2.78; p < 0.0001) and experimental autoimmune thyroiditis (EAT) mice (Ctrl 8.37 +/- 1.43, HT 55.82 +/- 2.87; p < 0.0001), accompanied by extensive thyroid follicular epithelial cell apoptosis in HT patients (Ctrl 32.16 +/- 1.79, HT 147.10 +/- 13.32; p < 0.0001) and EAT mice (Ctrl 66.78 +/- 6.72, HT 249.10 +/- 9.77; p < 0.0001). In vitro study showed that AOPPs induced reactive oxygen species (ROS) production via nicotinamide adenine dinucleotide phosphate oxidase (NOX), leading to apoptosis in human thyroid follicular epithelial cell (Nthy-ori 3-1). Treatment with apocynin, a NOX inhibitor, reduced AOPP-induced ROS production and apoptosis in Nthy-ori 3-1 cells, and in turn alleviated thyroid follicular epithelial cell apoptosis and autoimmune thyroiditis symptoms in mice. Mechanistically, AOPP treatment activated JNK pathway, leading to the downregulation of Bcl-2, upregulation of Bax, the mitochondrial membrane potential depolarization and consequently triggered the activation of mitochondria-dependent intrinsic apoptosis pathway. Collectively, our findings highlight the promotive roles of AOPP in HT and provide an attractive therapeutic target for HT therapy.

Background:Tumor deposits (TDs), nodules in the peritumoral adipose tissue with no architectural residue of lymph node, have previously been described in colorectal adenocarcinomas with poor prognosis. However, the significance of TD has not been fully investigated in patients with papillary thyroid carcinoma (PTC). Method:We retrospectively enrolled 541 patients undergoing surgery between 2015 and 2021. The patients were classified into two groups according to TD status (TD vs non-TD), and the clinicopathologic characteristics and disease-free survival (DFS) were compared. Associations of TD presence with other clinicopathologic factors were evaluated by logistic regression analysis. Univariate and multivariate Cox regression analyses were performed to determine the primary cohort's prognostic factors for DFS. A nomogram was constructed for clinicians as a quantitative tool for estimating DFS. Result:In our cohort, TD were identified in 16.1% of patients and had higher rate of aggressive features, including microscopic and gross extrathyroidal extension, invasion of the recurrent laryngeal nerve and esophagus, prevertebral fascia involvement or encasement of the carotid artery/internal jugular vein, extranodal extension, advanced clinical stage, tumor recurrence and distant metastasis (all P < 0.05). Univariate and multivariate Cox regression analyses confirmed TD as an independent prognostic factor for DFS, with a 2.501-fold increased risk of recurrence (P < 0.001). The nomogram, incorporating TD and other significant factors, demonstrated good discrimination and calibration (C-index = 0.79). Conclusion:The presence of TD was significantly associated with poor prognosis in PTC patients. TD showed promising efficacy as a potential prognostic indicator for PTC patients.

In a previous study, we proposed a modified technique for gasless transaxillary endoscopic total thyroidectomy (ETT) for patients with bilateral papillary thyroid carcinoma (PTC) using a single incision. Whether this method shows non-inferiority to the conventional open approach (COT) remains unclear. This study aims to investigate the safety and feasibility of ETT compared to COT in patients with PTC. We retrospectively analyzed the medical records of cT1-2 PTC patients who underwent total thyroidectomy between April 2020 and December 2022. All patients were diagnosed with bilateral PTC and categorized into ETT and COT groups based on the type of surgery. Propensity score matching (PSM) using nine clinicopathological characteristics was employed to compare the technical safety and short-term oncologic outcomes of ETT and COT, generating 45 pairs of matched patients to reduce potential selection bias. This study was followed by STROBE guideline. After PSM, 90 patients who underwent ETT (n = 45) or COT (n = 45) were included. Age, sex, tumor size, BMI, Hashimoto’s thyroiditis, multifocality, extrathyroidal extension, T-stage, and central compartment lymph node metastasis were not different between both groups. Both groups showed similar surgical outcomes, including lymph node yield, complications, and total medical costs. A few patients in each group experienced transient complications, all of which resolved within 6 months. No patients had permanent complications. Compared to COT, ETT with a modified technique offers excellent safety and acceptable short-term oncological outcomes in a selected cohort of patients with bilateral papillary thyroid carcinoma. ETT is a safe and feasible alternative to COT.

BACKGROUND:Anaplastic thyroid cancer (ATC) is the most aggressive thyroid malignancy and has an extremely poor prognosis, necessitating novel therapeutic strategies. This study investigated the role of anillin (ANLN) in ATC, focusing on its impact on tumor growth and metastasis through the RhoA/PI3K/AKT signaling pathway. METHODS:TCGA and GEO datasets were analyzed to identify key molecular alterations in thyroid cancer. ANLN expression was assessed in clinical samples. Functional assays, including CCK-8, colony formation, scratch, and Transwell invasion assays, and mouse xenograft models, were conducted to evaluate the biological role of ANLN. Coimmunoprecipitation, immunofluorescence, and active Rho GTPase pull-down assays, as well as phosphorylation antibody arrays, were used to explore the underlying mechanisms. RESULTS:Analysis of TCGA and GEO datasets revealed that ANLN is upregulated in thyroid cancers, including ATC and PTC, with higher ANLN expression correlating with worse survival outcomes. Functional studies demonstrated that ANLN promoted ATC cell proliferation, migration, and invasion. In vivo, ANLN knockdown inhibited tumor growth in xenograft models. Mechanistically, ANLN directly interacted with RhoA, facilitating its activation and subsequent stimulation of the PI3K/AKT signaling pathway. The tumorigenic effects of ANLN were suppressed by AKT inhibition with afuresertib or RhoA silencing. CONCLUSION:ANLN plays a crucial role in ATC progression by activating the RhoA/PI3K/AKT pathway, suggesting its potential as a therapeutic target in ATC.

Purpose Inflammation is recognized as a hallmark of Hashimoto’s thyroiditis (HT). Although inflammation is an important pathogenic factor that leads to thyroid follicular epithelial cell injury after HT, anti-inflammatory treatments remain controversial in the management of HT. Moreover, the molecular signatures involved in the pathophysiological changes that occur during the course of HT remain ambiguous.Methods The current study investigated the genes and pathways involved in HT by transcriptome sequencing analysis. Furthermore, western blot assays, ELISA and immunohistochemical staining were conducted to validate the expression levels of dysregulated proteins.Results HT was found to be associated with the enrichment of genes related to the inflammatory response, pyroptosis, and regulation of the lipid metabolic process. Further analysis revealed that genes associated with the interleukin (IL)-18 signaling pathway and the NLRP3 inflammasome were upregulated, and the expression levels of the IL-18, NLRP3, and APOC1 proteins were increased.Conclusion The transcriptome data obtained from HT patient samples revealed notable genes and pathways that may be novel therapeutic targets for the treatment of HT.

Background: Our objective was to assess the viability and oncological security of a gasless, transaxillary single-incision endoscopic procedure for performing total thyroidectomy and bilateral central neck dissection (TT + BCND). This study focused on patients diagnosed with bilateral papillary thyroid microcarcinoma (PTMC). Method: Between April 2020 and November 2021, 22 patients with bilateral PTMC underwent single-incision, gasless, transaxillary endoscopic TT + BCND. The patients’ clinicopathologic characteristics, surgical completeness and complications were analyzed. Result: Single-incision, gasless, transaxillary endoscopic TT + BCND was successful performed in all patients. The median (IQR) total surgical time was 143 (85–160) min. Only two patients experienced transient unilateral RLN palsy or transient hypocalcemia. All these complications resolved within 1 month after surgery. The median duration of hospital stay after surgery was 4 (3–4.5) days. The median hospitalization expense for these patients was 3848 (3781–4145) USD. The median number of lymph node yielded was 10.5 (8–15). The cosmetic outcomes were well-received by all individuals. Conclusion: In certain cases, gasless, transaxillary endoscopic TT + BCND procedure performed through a single incision proved to be a secure alternative for managing bilateral PTMC.

Objective: To evaluated the safety and feasibility of dissection of lymph nodes posterior to right recurrent laryngeal nerve (ⅥB compartment) in endoscopic thyroidectomy through gasless axillary posterior approach. Methods: A total of 350 cases with right lobe papillary thyroid carcinoma (PTC) who underwent endoscopic lobectomy, isthmusectomy and central compartment neck dissection via gasless axillary posterior approach based at the Department of General Surgery, Nanfang Hospital, Southern Medical University from June 2020 to December 2022 were retrospectively analyzed. Summarize the clinical, pathological characteristics, and postoperative complications of the patients. SPSS 25.0 was used for statistical analysis of the data. Results: All 350 patients underwent endoscopic surgery successfully, with no conversion to open surgery. There were 303 females and 47 males, with an average age of (36.3±9.2) years. Of those, 287 patients were in pT1a stage, 62 in pT1b stage, and one patient in pT2 stage. There was no T3 or T4 stage patient. The mean numbers of yielded lymph nodes in right central compartment and ⅥB compartment were 8.11±4.65 (range, 1-31) and 2.62±1.86 (range, 1-12), respectively. ⅥB compartment metastasis was detected in 52 (14.86%) of 350 patients. The incidence of transient recurrent laryngeal nerve injury was 0.86%(3/350). Postoperative hematoma occurred in three patients (0.86%). Conclusion: The dissection of ⅥB compartment in endoscopic thyroidectomy through gasless axillary posterior approach is safe and feasible in selected PTC patients.

随着腔镜甲状腺手术的发展及推广,经腋窝腔镜甲状腺手术无疑被证实是一种安全、可行的手术方式.其中,经腋窝无充气后入路腔镜甲状腺手术(GTPET)因无充气干扰的清晰视野,已被广泛接纳并采用.但因其侧面观视角、镜头与器械共用手术空间的特点,使手术操作存在固有难点.为解决腔镜操作中视角配合问题,有团队应用扶镜机器人,但对于GTPET这种操作范围较小的手术方式,手术视角及操作仍依赖于术者及扶镜手的配合.为克服GTPET操作中的难点,笔者引入"场景化"操作理念,从扶镜手的角度出发,通过三部分规范GTPET手术过程中扶镜手的操作流程.一为手术前准备:规范患者体位摆放及扶镜手位置;二为扶镜手操作要点:概括为"一支点""二入路""三平行";三为"四宫格"法镜下视野场景化辅助操作:将手术区域划分为I～Ⅳ区,据此引导手术操作.

Objective To investigate the safety and effectiveness of establishing a transaxillary lumpectomy space for lumpectomy thyroid surgery without inflatable posterior approach based on the deep cervical fascial anatomy.Methods The clinical data of 276 consecutive patients admitted to the Department of Thyroid Hernia Surgery,Southern Hospital of Southern Medical University from June to December 2021 who underwent transaxillary lumpectomy thyroid surgery were retrospectively analyzed,and the surgical space was established based on fascial anatomy.Intraoperative and postoperative conditions were observed and recorded,and follow-up was performed on the second day after surgery and at 3 and 6months after surgery.Results The operative time was 80.5（60-115） min and the operative space was established in 18（12-26） min.Intraoperative bleeding was 5（1-15） mL.There were 2 cases of intraoperative extra-jugular venous and genera expenditure blood and 1 case of intraoperative anterior jugular vein bleeding.The postoperative hospital stay was 2.5（1-4） d.Sensory recovery scores in the clavicular region were assessed on the second postoperative day:221（80.1%） S3,55（19.9%） S2,no S4,S3+,S1 or S0 cases;3 months postoperatively:245（88.8%） S3+/S4,30（10.9%） S3 and 1（0.4%） S2;6 months postoperatively:270（97.8%） S3+/S4,6（2.2%） S2,no postoperative flap area effusion.Follow-up was completed in all cases.Two patients had temporary hoarseness after surgery and voice was restored at the 3-month postoperative follow-up.There were no postoperative lymphatic fistulas,Horner’s syndrome,postoperative bleeding or swelling of the sternocleidomastoid muscle,and no recurrent cases.Conclusion The fascial anatomy-based method of transaxillary uninflated lumpectomy thyroid surgery space creation is safe and effective and can be used as a routine method.

BackgroundEndoscopic thyroidectomy (ET) via gasless unilateral axillary (GUA) approach has been widely implemented worldwide. Based on our concept of mesothyroid excision in open surgery, we proposed a novel anatomy-based five-settlement method in ET via the GUA approach. This preliminary report aimed to explore the efficacy and safety of this method in patients with papillary thyroid carcinoma (PTC).MethodsPTC patients who underwent endoscopic ET and unilateral central compartment neck dissection (CCND) via GUA approach with the five-settlement method at the Department of General Surgery, Nanfang Hospital, Southern Medical University from March 2020 to December 2021 were retrospectively collected. The data included general clinicopathological characteristics, surgical information (including duration, complication, and clinicopathological features), and hospital stay information, and other medical records were documented.ResultsIn total, 521 patients underwent lobectomy and CCND under the GUA approach with the five-settlement method. The mean number of lymph nodes yielded (LNY) and positive lymph nodes (PLN) was 5.7 ± 4.3 (range, 1–30) and 1.0 ± 1.8 (range, 0–12), respectively. The incidence of transient recurrent laryngeal nerve injury was 1.1%. Chyle leakage and Horner’s syndrome respectively occurred in one patient (0.2%). Five (0.9%) patients developed a hematoma. No severe complications or conversion to open surgery have occurred.ConclusionThe five-settlement method could be implemented safely and efficiently in ET+CCND via the GUA approach in selected PTC patients.

Our video demonstrates a modified gasless transaxillary endoscopic thyroid surgery with the posterior approach for bilateral low-risk thyroid cancer. In this paper, we provided a detailed introduction to the right gasless transaxillary endoscopic total thyroidectomy surgical procedure for bilateral low-risk thyroid cancer, and briefly summarized the Lei's seven-sinking method: sinking the clavicular head of the sternocleidomastoid muscle (CHSCM); sinking the cervical vascular sheath; sinking the right wall of the esophagus; sinking the right recurrent laryngeal nerve (RLN); sinking the trachea; sinking the left RLN and sinking the thyroid. A 5-cm incision was made starting from the anterior axillary line along the natural fold at the axilla. A trocar was placed in the axillary incision approximately 3-5 cm away from the side of the breast and slightly below the anterior axillary line. Using blunt dissection and electrocautery, a working space was created by elevating a subcutaneous flap above the pectoralis major muscle. The thyroid bed was accessed through the two heads of the SCM, and then the thyroid was separated from the strap muscles. Thyroidectomy and central lymph node dissection were fully endoscopically performed with the posterior approach using conventional endoscopic instruments. Through the posterior approach and the operation steps of the seven-sinking method, total thyroidectomy and bilateral central lymph node dissection can be achieved relatively easily.

Background In a previous study, we proposed a novel anatomy-based five-settlement method for transaxillary endoscopic thyroidectomy (fs-TAT) for patients with papillary thyroid carcinoma. The safety of this new method has been reported in a retrospective study of a single cohort. The safety and short-term oncological outcome of this method was confirmed by comparing it with conventional open surgery (COT) in patients with papillary thyroid microcarcinoma. Methods The medical records of patients who underwent fs-TAT or COT by a single surgeon from February 2019 to December 2021 were reviewed retrospectively. All patients were diagnosed with papillary thyroid microcarcinoma and underwent lobectomy and ipsilateral central compartment neck dissection. Propensity score matching was used to compare the technical safety and short-term oncologic outcomes of fs-TAT and COT for the purpose of reducing potential selection bias. Reporting was consistent with the STROCSS 2021 guidelines. Result After propensity score matching, 460 (fs-TAT: 230; COT: 230) patients remained in the study population. There were no significant differences in sex, age, tumor size, Hashimoto’s thyroiditis, or tumor multifocality between the groups. The operative time was longer [104.5 (90.3, 120.0) vs. 62.0 (52.0, 76.0), P < 0.001] and the total postoperative drainage volume [135(90, 210) vs. 75 (55, 115), P < 0.001] was greater in the fs-TAT group than in the COT group. However, intraoperative bleeding [3.0 (2.0, 5.0) vs. 5.0 (5.0, 7.5), P < 0.001] was greater, and the median number of lymph nodes yielded [5.0 (2.3, 8.0) vs. 7.0 (5.0, 11.0), P < 0.001] was greater in the COT group than in the fs-TAT group. The groups exhibited no significant difference in the rate of complications (fs-TAT: 2.2% vs. COT: 2.6%, P = 0.856), rate of positive lymph nodes (fs-TAT: 32.2% vs. COT: 36.5%, P = 0.377), length of postoperative hospital stay (3 days vs. 3 days, P = 0.305) or total medical costs (26,936 vs. 26,549, P = 0.144). Conclusion Compared to conventional open surgery, fs-TAT offered excellent safety and acceptable short-term oncological outcomes in a selected cohort of patients with papillary thyroid microcarcinoma.

BACKGROUND:This study aimed to evaluate the relationship between lateral lymph node yield (LLNY) and the ratio of lateral positive lymph nodes to lymph node yield (LPLR) from initial lateral neck dissection (LND) in patients with papillary thyroid carcinoma (PTC), as well as the risk of recurrence in patients undergoing LND reoperations.METHODS:This retrospective cohort study enrolled patients with PTC who underwent revision LND between 1 January 2012, and 31 December 2021. The initial and revised clinical data were retrieved. Patient demographics, clinicopathological features, clinical records, and follow-up information were also reviewed. LLNY and LPLR were determined during the initial LND.RESULTS:In total, 156 patients with PTC were included in this study, with a median follow-up of 36.5 months; 107 had recurrent lateral neck disease. The optimal LLNY and LPLR cutoff values for recurrent/persistent disease were 24.5 and 32.74%, respectively. The high-risk group (LLNY<25) had the lowest recurrence-free survival rate compared with to moderate-risk group (LLNY≥25, LPLR≥32.74%) and low-risk group (LLNY≥25, LPLR<32.74%) ( P <0.001). The moderate-risk group had lower recurrence-free survival than the low-risk group. Multivariate analysis revealed that an LLNY less than 25 in the initial LND was an independent risk factor for recurrence/persistence of lateral neck ( P <0.001).CONCLUSIONS:This study identified that LLNY and LPLR were associated with recurrence/persistence in PTC patients at the time of revision surgery was performed.

BackgroundTransaxillary gasless endoscopic thyroidectomy (TGET) is a widely performed operation, but its side view angle and instrument interference have caused concerns for most surgical groups. The aim of this study was to introduce scene-guided camera assistance (SGA) and analyze its role in facilitating TGET.MethodsWe put forward key points for camera holders, including one pivot, two positions, and three planes, and separated TGET operations into five parts. We also established the view angle for each part of the operation for the camera holder to follow. Then, we reviewed 416 patients who underwent TGET with or without SGA and analyzed their demographic characteristics, operative outcomes, pathologic outcomes, and early complications.ResultsThe TGET and TGET-SGA groups were similar in terms of age, sex ratio, height, weight, tumor size, Hashimoto’s thyroiditis ratio, and cN1 ratio. The operation time and postoperative hospital stay were significantly longer in the TGET group than in the TGET-SGA group (114.43 ± 17.20 minutes vs. 101.82 ± 19.39 minutes and 3.16 ± 0.77 days vs. 2.16 ± 0.55 days, respectively, P < 0.001). The account of retrieved lymph nodes was less in the TGET group than in the TGET-SGA group (5.61 ± 4.27 vs. 6.57 ± 4.96, P = 0.038).ConclusionSGA provided guidance for camera holders, and the data showed that it was an improvement for TGET operations.

Gasless transaxillary posterior endoscopic thyroidectomy (GTPET) is a new approach for thyroid cancer. It allows en bloc resection of the thyroid and central lymph nodes. Few studies have reported on the learning curve for GTPET.We examined the learning curve of GTPET for thyroid cancer by cumulative sum (CUSUM) analysis by retrospectively analyzing patients who underwent hemithyroidectomy with ipsilateral central neck dissection between December 2020 and September 2021 at a tertiary medical center, including the first patient. Moving average analysis and sequential time-block analysis were used for validation. Data on the clinical factors between the two periods were compared. In the overall cohort, the average time for GTPET for thyroid cancer was 113.25 min to harvest an average of 6.4 central lymph nodes. The CUSUM curve of the operative time indicated an inflection point after 38 patients. Moving average analysis and sequential time-block analysis validated the number of procedures needed for GTPET proficiency. (124.05 min vs. 107.63 min for the unproficient period vs. proficient period, respectively; P < 0.001) The number of retrieved lymph nodes was not associated with a certain level of proficiency per the learning curve. The main complication during the surgeon’s unproficient period was transient hoarseness (3/38), which was similar to that in their proficient period (2/73, p = 0.336). Proficiency in GTPET is associated with performing more than 38 procedures. Standard course training and instruction on careful management are required prior to introducing the procedure.

Abstract Background Transaxillary endoscopic thyroidectomy has been introduced to achieve better cosmetic outcomes. However, the benefits of this technology on the patients’ health‐related quality of life (HRQoL) remain unclear. We aimed to investigate whether transaxillary endoscopic lobectomy is comparable to conventional open lobectomy in terms of QOL and cosmetic results in order to provide more evidence for establishing appropriate clinical decisions. Methods Between August 2019 and May 2020, transaxillary endoscopic lobectomy and conventional open lobectomy were performed in 73 and 99 patients with papillary thyroid microcarcinoma, respectively. HRQoL was assessed at 1, 3, 6, and 12 months after surgery using the Thyroid Cancer‐Specific Quality of Life Questionnaire. The cosmetic outcomes were assessed 12 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS). Results No significant difference was observed in the surgical results between the two groups. However, the data showed that the average operative time and postoperative hospital stay of the transaxillary group were longer than those of the open group (p < 0.001). Both groups showed similar changes in the QOL scores over time. However, the transaxillary group had fewer complaints of the throat or oral problems at 1 month postoperatively than the open group (p < 0.001). During the follow‐up, the cosmetic results of scars in the transaxillary group were significantly better than those in the open group (p < 0.05). Patients who underwent transaxillary endoscopic lobectomy had higher overall satisfaction with their scar appearance, determined using POSAS, at 12 months postoperatively. Conclusions The current findings suggest that transaxillary endoscopic lobectomy may offer better cosmetic and HRQoL outcomes.

Excessive keratinocyte apoptosis leads to impaired wound healing. Recently, advanced oxidation protein products (AOPP) have been recognized as a marker of oxidative stress and a potent inducer of apoptosis. Previously, we have demonstrated that extracellular AOPP accumulation induced keratinocyte apoptosis, and we discovered that autophagy was involved. To further elucidate the role and mechanism of autophagy in AOPP-induced-apoptosis of keratinocytes, we treated HaCaT cells with increasing concentrations of AOPP-human serum albumin or with AOPP-human serum albumin for increasing durations. Cyto-ID solution staining was used to assess cell autophagy using confocal laser scanning microscopy. Autophagy-related protein interactions were investigated using western blot analysis. Exposure of HaCaT cells to AOPP decreased the expression of mammalian target of rapamycin (mTOR) and increased the expression of autophagy-related proteins Beclin-l and LC3, and eventually led to autophagy. Furthermore, an autophagy agonist significantly decreased the expression of apoptosis-related proteins. Taken together, we showed that accumulation of extracellular AOPP induced autophagy in HaCaT cells via a reactive oxygen species-dependent, mTOR-Beclin-1-mediated pathway, and that excessive autophagy-mediated apoptosis, which resulted in delayed wound healing.

Neuroinflammation is recognized as a hallmark of spinal cord injury (SCI). Although neuroinflammation is an important pathogenic factor that leads to secondary injuries after SCI, neuroprotective anti-inflammatory treatments remain ineffective in the management of SCI. Moreover, the molecular signatures involved in the pathophysiological changes that occur during the course of SCI remain ambiguous. The current study investigated the proteins and pathways involved in C5 spinal cord hemi-contusion injury using a rat model by means of 4-D label-free proteomic analysis. Furthermore, two Gene Expression Omnibus (GEO) transcriptomic datasets, Western blot assays, and immunofluorescent staining were used to validate the expression levels and localization of dysregulated proteins. The present study observed that the rat models of SCI were associated with the enrichment of proteins related to the complement and coagulation cascades, cholesterol metabolism, and lysosome pathway throughout the acute and subacute phases of injury. Intriguingly, the current study also observed that 75 genes were significantly altered in both the GEO datasets, including ANXA1, C1QC, CTSZ, GM2A, GPNMB, and PYCARD. Further temporal clustering analysis revealed that the continuously upregulated protein cluster was associated with immune response, lipid regulation, lysosome pathway, and myeloid cells. Additionally, five proteins were further validated by means of Western blot assays and the immunofluorescent staining showed that these proteins coexisted with the F4/80+ reactive microglia and infiltrating macrophages. In conclusion, the proteomic data pertaining to the current study indicate the notable proteins and pathways that may be novel therapeutic targets for the treatment of SCI.